H1N1 Q226R In Mississippi

The recent high frequency of severe and fatal H1N1 cases in Texas has raised considerable concern. H1N1 frequencies are approaching 100% in Texas and throughout the United States. The highest levels of influenza like illness (ILI) has been reported in the south (TX, LA, MS, AL) and the number of patients on ECMO machines in Austin has raised concerns that these serious cases could severely tax health care delivery. ECMO machines are resource dense and in limited supply. 5 adults (aged from 20’s to 50’s) on ECMO machines at one institution maxed out the resources (although one is kept in reserve to address potential mechanical problems).

The CDC has been releasing a small set of H1N1 sequences every 2-3 weeks. Included were oseltamivir resistant (H274Y) sequences from Louisiana, Mississippi, and Utah, which could seriously limit Tamiflu treatment, even if present as a minority species.

Receptor binding domain changes which target the lung via gal 2,3 receptors could lead to the lung damage being reported for young and middle aged adults, including pregnant women with severe or fatal pneumonia. D225G was present in summer sequences from Florida (A/Florida/13/2013 and A/Florida/16/2013) and Utah, A/Utah/08/2013.

However, more recent sequences from October collections from patients (10M and 29M) in Mississippi (A/Mississippi/09/2013 and A/Mississippi/10/2013) have raised similar concerns for Q226R, which also targets gal 2.3 receptors. Virus isolated on eggs (which selects for D225G and/or Q226R) had Q226R, while virus isolated on mammalian cells had Q226 (all other positions on H1, N1, and MP were identical for each set).

These mixtures raise concerns that H1N1 can form pseudotypes with Q226 on the H1 for transmission, and Q226R on H1 for expansion in the lower respiratory tract. Most of the public H1N1 sequences are from mammalian isolates, raising concerns that D225G and Q226R are more common than indicated by sequences in public database.